Cystic fibrosis patients suffer chronic bacterial infections and colonization in the lung, as well as the consequent neutrophil dominated inflammatory response. An imbalance is created between protease and anti-protease levels in the lung and the unrestricted actions of the neutrophil proteases are responsible for the deterioration of pulmonary function and much of the morbidity and mortality associated with this disease. Human monocyteineutrophil elastase inhibitor (M/NEI) is a novel and efficient inhibitor of the major neutrophil proteases: elastase, proteinase-3 and cathepsin G. M/NEI is a member of the serpin superfamily, closely related to plasminogen activator. Recombinant M/NEI has been produced at pilot scale and is well characterized. A biochemically integrated series of preclinical studies has established the therapeutic potential of rM/NEI for cystic fibrosis patients. Cystic fibrosis is a chronic disease, requiring aerosol treatments several times per day, every day, throughout the patient's lifetime. The overall goal of this project is to develop a convenient dry powder drug and device to control protease mediated lung destruction. This Phase I project will successfully conclude with evidence that: (1) rM/NEI can be formulated as a dry powder and (2) rM/NEI aerosol can mitigate neutrophil dominated inflammatory lung injury. PROPOSED COMMERCIAL APPLICATIONS: Aerosol treatment for prevention of elastase-induced damage in inflammatory lung diseases such as cystic fibrosis, emphysema, respiratory distress syndrome, asthma and chronic bronchitis, is estimated to exceed a 1 billion-dollar per year domestic market. The Center for Blood Research has secured broad patent protection for rM/NEI.